Jibreel Jumare

Associations between Cognition, Gender and Monocyte Activation among HIV Infected Individuals in Nigeria

The potential role of gender in the occurrence of HIV-related neurocognitive impairment (NCI) and associations with markers of HIV-related immune activity has not been previously examined. In this study 149 antiretroviral-naïve seropositive subjects in Nigeria (SP, 92 women and 57 men) and 58 seronegative (SN, 38 women and 20 men) were administered neuropsychological testing that assessed 7 ability domains. From the neuropsychological test scores was calculated a global deficit score (GDS), a measure of overall NCI. Percentages of circulating monocytes and plasma HIV RNA, soluble CD163 and soluble CD14 levels were also assessed. HIV SP women were found to be younger, more educated and had higher CD4+ T cell counts and borderline higher viral load measures than SP men. On the neuropsychological testing, SP women were more impaired in speed of information processing and verbal fluency and had a higher mean GDS than SN women. Compared to SP men, SP women were also more impaired in speed of information processing and verbal fluency as well as on tests of learning and memory. Numbers of circulating monocytes and plasma sCD14 and sCD163 levels were significantly higher for all SP versus all SN individuals and were also higher for SP women and for SP men versus their SN counterparts. Among SP women, soluble CD14 levels were slightly higher than for SP men, and SP women had higher viral load measurements and were more likely to have detectable virus than SP men. Higher sCD14 levels among SP women correlated with more severe global impairment, and higher viral load measurements correlated with higher monocyte numbers and sCD14 and sCD14 levels, associations that were not observed for SP men. These studies suggest that the risk of developing NCI differ for HIV infected women and men in Nigeria and, for women, may be linked to effects from higher plasma levels of HIV driving activation of circulating monocytes.

Once-daily antiretroviral therapy among treatment-experienced Muslim patients fasting for the month of Ramadan

Many countries with a considerable burden of human immunodeficiency virus (HIV) infection in Africa and Asia also have a substantial Muslim population. Anti-retroviral therapy (ART) has led to reductions in HIV morbidity and mortality in those areas. However, for ART to remain durably effective its provision should be adapted to local and religious customary practices such as Ramadan fasting. The fasting is often observed by Muslims with HIV infection and ART might be compromised by sub-optimal adherence during fasting as it precludes the ingestion of oral substances during the daytime and is often associated with an alteration of meals/sleeping patterns. We studied once-daily compared to twice-daily dosed ritonovir boosted lopinavir with fixed-dose tenofovir-emtricitabine once-daily among 17 heavily treatment-experienced stable FT patients in Nigeria. No changes in adherence, diarrhoea, CD4 cell counts, viral load, haematocrit, kidney, liver and lipid tests were observed. Effectiveness, safety and tolerability appeared unaffected by the changes.

Chloroquine-Azithromycin Combination Antimalarial Treatment Decreases Risk of Respiratory- and Gastrointestinal-Tract Infections in Malawian Children

BACKGROUND Chloroquine-azithromycin is being evaluated as combination therapy for malaria. It may provide added benefit in treating or preventing bacterial infections that occur in children with malaria. OBJECTIVE We aim to evaluate the effect of treating clinical malaria with chloroquine-azithromycin on the incidence of respiratory-tract and gastrointestinal-tract infections compared to treatment with chloroquine monotherapy. METHODS We compared the incidence density and time to first events of respiratory-tract and gastrointestinal-tract infections among children assigned to receive chloroquine-azithromycin or chloroquine for all symptomatic malaria episodes over the course of 1 year in a randomized longitudinal trial in Blantyre, Malawi. RESULTS The incidence density ratios of total respiratory-tract infections and gastrointestinal-tract infections comparing chloroquine-azithromycin to chloroquine monotherapy were 0.67 (95% confidence interval [CI], .48, .94) and 0.74 (95% CI, .55, .99), respectively. The time to first lower-respiratory-tract and gastrointestinal-tract infections were significantly longer in the chloroquine-azithromycin arm compared to the chloroquine arm (P = .04 and P = .02, respectively). CONCLUSIONS Children treated routinely with chloroquine-azithromycin had fewer respiratory and gastrointestinal-tract infections than those treated with chloroquine alone. This antimalarial combination has the potential to reduce the burden of bacterial infections among children in malaria-endemic countries.

Proceedings from the NIMH symposium on “NeuroAIDS in Africa: neurological and neuropsychiatric complications of HIV”

Despite major advances in HIV-1 treatment, the prevalence of HIV-associated neurocognitive disorders (HAND) remains a problem, particularly as individuals on suppressive treatment continue to live longer. To facilitate discussion on emerging and future directions in HAND research, a meeting was held in Durban, South Africa in March 2015 as part of the Society of Neuroscientists of Africa (SONA) conference. The objective of the meeting was to assess the impact of HIV subtype diversity on HAND and immunological dysfunction. The meeting brought together international leaders in the area of neurological complications of HIV-1 infection with special focus on the African population. Research presentations indicated that HAND was highly prevalent and that inflammatory cytokines and immune-activation played important roles in progression of neurocognitive impairment. Furthermore, children on antiretroviral therapy were also at risk for developing neurocognitive impairment. With respect to the effect of HIV-1 subtype diversity, analyses of HIV-1 clade C infection among South Africans revealed that clade C infection induced cognitive impairment that was independent of the substitution in HIV-1 Trans-Activator of Transcription (Tat; C31S). At the cellular level, a Zambian study showed that clade C infection resulted in reduced brain cell death compared with clade B infection suggesting clade specific variations in mediating brain cell injury. Furthermore, ex vivo Tat protein from clade CRF02_AG, prevalent in West/ Central Africa, exhibited reduced disruption of brain endothelium compared with clade B Tat protein. Discussions shed light on future research directions aimed at understanding biomarkers and disease mechanisms critical for HAND.

Antiretroviral Drugs Alter the Content of Extracellular Vesicles from HIV-1-Infected Cells

To date, the most effective treatment of HIV-1 is a combination antiretroviral therapy (cART), which reduces viral replication and reverses pathology. We investigated the effect of cART (RT and protease inhibitors) on the content of extracellular vesicles (EVs) released from HIV-1-infected cells. We have previously shown that EVs contain non-coding HIV-1 RNA, which can elicit responses in recipient cells. In this manuscript, we show that TAR RNA levels demonstrate little change with the addition of cART treatment in cell lines, primary macrophages, and patient biofluids. We determined possible mechanisms involved in the selective packaging of HIV-1 RNA into EVs, specifically an increase in EV-associated hnRNP A2/B1. More recent experiments have shown that several other FDA-approved drugs have the ability to alter the content of exosomes released from HIV-1-infected cells. These findings on cART-altered EV content can also be applied to general viral inhibitors (interferons) which are used to treat other chronic infections. Additionally, we describe unique mechanisms of ESCRT pathway manipulation by antivirals, specifically the targeting of VPS4. Collectively, these data imply that, despite antiretroviral therapy, EVs containing viral products are continually released and may cause neurocognitive and immunological dysfunction.

Cognitive Function Among Antiretroviral Treatment–Naive Individuals Infected With Human Immunodeficiency Virus Type 1 Subtype G Versus CRF02_AG in Nigeria

Background Human immunodeficiency virus type 1 (HIV-1) subtype has been shown to be associated with disease progression. We compared cognitive function between individuals infected with HIV-1 subtype G and CRF02_AG in Nigeria. Methods For this cross-sectional study, samples were analyzed from 146 antiretroviral-naive participants. Genotypic analysis of plasma HIV RNA was performed by nested polymerase chain reaction of protease and reverse transcriptase genes, and sequences were aligned with curated HIV-1 subtype references. Cognitive status was determined using demographically adjusted T scores and global deficit score (GDS) obtained from a comprehensive neuropsychological test battery. Results A total of 76 (52.1%) participants were infected with CRF02_AG, 48 (32.8%) with subtype G, and 22 (15.1%) with other HIV-1 strains. In a multivariable linear regression adjusting for plasma HIV RNA, CD4 count, and depression score, mean global T score was lower among subtype G-infected compared with CRF02_AG-infected participants (mean difference, -3.0 [95% confidence interval {CI}, -5.2, to -.7]; P = .011). Also, T scores were significantly lower among subtype G- than CRF02_AG-infected participants for the speed of information processing, executive function, and verbal fluency ability domains. Adjusting for similar variables in a logistic regression, the odds of global cognitive impairment (GDS ≥0.5) were 2.2 times higher among subtype G compared with CRF02_AG-infected participants (odds ratio, 2.2 [95% CI, .9-5.4]; P = .078). Conclusions Cognitive performance was significantly worse among antiretroviral-naive individuals with HIV-1 subtype G vs CRF02_AG infection. Further studies are required to characterize the mechanistic basis for these differences.

P-D15 Peripheral blood lymphocyte HIV DNA levels correlate with HIV associated neurocognitive disorders

Introduction:Mononuclear cells play a key role in facilitating the pathogenic mechanisms leading to HIV associated neurocognitive disorders (HAND). We examined the association between levels of HIV DNA within monocytes and lymphocytes and HAND. Method:Blood samples were obtained from 40 antiretroviral naive participants in Nigeria. CD14+ cells and T&B lymphocytes were isolated from peripheral blood mononuclear cells by bead separation (84-98% purity for CD14+ cells). Total HIV DNA was quantified using real-time PCR assay targeting HIV LTR-gag and cell input numbers determined by the number of CCR5 copies/sample. Utilizing a 7-domain neuropsychological test battery and activities of daily living assessment, participants were classified as either unimpaired, having asymptomatic neurocognitive impairment (ANI), minor neurocognitive disorder (MND), or HIV associated dementia (HAD) in line with the Frascati criteria. Results:The mean log10 HIV DNA copies/106 cells were higher for T & B lymphocytes than for CD14+ monocytes (P-value: 0.0002). In a multivariable linear regression adjusting for CD4 count, viral load and lymphocyte count, compared to unimpaired individuals, the mean copy numbers for T & B lymphocytes were higher among those with HAND (P-value: 0.01) and for those with MND [P-value: 0.02 (Tukey adjusted: 0.07)]. In a multivariable logistic regression adjusting for same variables, the odds of cognitive impairment was 6.7 times greater per log increase in HIV DNA within T & B lymphocytes (P-value: 0.02). There was no significant association between cognitive impairment and HIV DNA within CD14+ monocytes. Conclusions:In this cohort we found a strong association between levels of cell-associated HIV DNA within the lymphocyte subset and HAND. Further studies looking at similar association among patients with suppressed viremia are required for inference on integrated DNA.

Adherence to Highly Active Antiretroviral Therapy among HIV-Infected Children in Kano, Nigeria

Background: HIV has emerged as one of the leading causes of childhood mortality and morbidity in sub Saharan Africa. Antiretroviral therapy (ART) in children in Africa has resulted in dramatically improved survival. However, excellent adherence is one of the most important factors in determining treatment success and preventing viral resistance. While studies of African adults showed that good adherence to ART is possible despite poor social circumstances, there are limited data on ART adherence among African children, and hence the need for the current study. This study determined factors associated with adherence to highly active antiretroviral therapy (HAART) among HIV-infected children in Kano, Nigeria. Method: A cross-sectional study was conducted at the Special Treatment Clinic (STC) of Aminu Kano Teaching Hospital, Kano, Nigeria. The study population comprised HIV- infected children taking ARV medications, which accessed care at the Clinic between June and August 2010, and met the eligibility criteria. A list of all children who were on HAART and had a clinic appointment within the study period was generated. From this list, participants were randomly selected using a computer-based random number generator. Caregivers were interviewed at the clinic using a structured questionnaire Results: A total of 122 children (64% males) out of 130 contacted, whose caregivers provided consent, were recruited into the study. The median age of the study children was 5.5 years (IQR: 1.3 to 14 years). A total of 80 children (65.6%) were adherent to the prescribed antiretroviral drugs for the 7 days preceding the interview. Non-adherence was found to be significantly associated with caregivers report of missing at least one clinic appointment in the last six months (p-value 0.000) and children on second line HAART regimen (p-value 0.01). However, children whose caregivers were older than 25 years (p-value 0.012) were more likely to be adherent than their respective counterparts. Conclusion: Adherence to HAART in children in Kano, Nigeria was similar to reported adherence levels from other sub-Saharan African countries. Keeping clinic appointments was strong predictor of good adherence to HAART.